Molecular mechanisms underlying enzyme development in differentiating tissues are under study, employing the postnatal development and hormonal control of rat liver and epidermal histidase as a model system. Neonatally administered androgen (NA) was ineffective in masculinizing the subsequent development of hepatic histidase in females, an imprinting phenomenon observed with other similarly regulated enzymes. However, in males, NA modified epidermal and hepatic histidase activity, in a manner simulating prepubertal orchiectomy. Indeed, testosterone or dihydrotestosterone, administered during the first three neonatal days, elicited: profound suppression of testicular growth, spermatogenesis, and androgen secretion; infertility; and marked reduction in serum gonadotrophin levels in adulthood following castration. Both testes and pituitaries were capable of stimulation by gonadotrophins and GnRH, respectively. Thus, either differentiation of androgen suppressible hypothalamic (or higher brain) centers, responsible for subsequent tonic gonadotrophin secretion, or transient vulnerability of these centers to exogenous androgen occurs during a limited neonatal period in the male. Studies have been initiated on the development and hormonal control of the expression of the histidase gene, by quantitation of histidase messenger RNA and evaluation of its translation product. Anti-histidase immunoprecipitation of the translational products, derived from rat liver poly-A rich RNA directed translation in a wheat germ system, yielded polypeptide fragments of lower molecular weight than in vivo elaborated subunit. These immunoprecipitable fragments are either true translational products, prematurely released histidase polypeptide chains or contaminants. These alternatives are currently being explored in the rabbit reticulocyte translational systems.